Carthadex trial

Patients with Multiple Myeloma, ISS stage I -III age 18-65 yrs (must be transplant candidates) at first presentation; 145 patients.

Study design:
For patient numbers 111 to 145:

Induction treatment (before HDM/ASCT):
Carfilzomib 20mg/m2 for days 1,2, then 56mg/m2 days 8,9,15,16 of cycle 1, then 56mg/m2 throughout next cycles.
Thalidomide 200 mg days 1-28 of a 28 day cycle.
Dexamethasone 20 mg days 1,2,8,9,15,16 of a 28 day cycle.
8 cycles.

Consolidation treatment (guideline 8 weeks after HDM/ASCT):
Carfilzomib 56mg/m2 days 1,2,8,9,15,16 of a 28 day cycle.
Thalidomide 50 mg days 1-28 of a 28 day cycle.
Dexamethasone 20 mg days 1,2,8,9,15,16 of a 28 day cycle.
4 cycles.

Inclusion criteria

• Patients with a confirmed diagnosis of multiple myeloma stage I to III according to the ISS criteria (see appendix I);
• Age 18-65 years inclusive;
• WHO performance status 0-3 (WHO=3 is allowed only when caused by MM and not by co-morbid conditions) (see appendix II);
• Negative urine pregnancy test at inclusion if applicable;
• Written informed consent.

Exclusion Criteria

• Known intolerance of Thalidomide;
• Systemic AL amyloidosis;
• Non-secretory MM;
• Waldenstrom’s macroglobulinemia or IgM MM;
• Previous chemotherapy or radiotherapy except 2 cycles of Melphalan/Prednisone
• or local radiotherapy in case of local myeloma progression;
• Severe cardiac dysfunction (NYHA classification II-IV, see appendix III);
• Severe pulmonary dysfunction;
• Significant hepatic dysfunction (serum bilirubin  30 mol/l or transaminases  3.0 times normal level), unless related to myeloma;
• Creatinine clearance <15 cc/min;
• Alkaline Phosphatase >3x ULN;
• ANC < 1,0 x10⁹/L, platelets < 75 x10⁹/L, Hb < 4.9 mmol/L;
• Intolerance to thromboprophylaxis;
• Patients known to be HIV-positive;
• Patients with active, uncontrolled infections;
• Patients with neuropathy, CTC grade 3 or higher or grade 2 painful peripheral neuropathy;
• Patients with a history of active malignancy during the past 5 years with the exception of basal carcinoma of the skin or stage 0 cervical carcinoma;
• Patients (all males and all pre-menopausal women) who are not willing or capable to use adequate contraception during the therapy;
• Lactating women;
• WHO Performance status > 3.